One of the objectives of this research is to study the overall process of lipoprotein production and the effects of metabolic and hormonal perturbations on this process. The isolated perfused livers of normal rats and rats subjected to various metabolic perturbations will be used in conjunction with procedures (a) to characterize rates of secretion and density distributions of apoproteins, and (b) to characterize the apoprotein compositions of isolated lipoproteins. These procedures include ultracentrifugation, electron microscopy, and electrophoretic procedures and radioimmunoassays for apoproteins. Another aim is to describe the intracellular processes of lipoprotein synthesis and assembly, specifically to localize where in the cell in relation to each other various appproteins are synthesized, and where lipid and apoprotein assembly occurs. Immunohistochemical techniques suitable for electron microscopy will be developed for these experiments. It is hoped that the information gained from this model system will lead to a better understanding of lipoprotein metabolism and to the design of more effective measures for the control of lipoprotein disorders in man. Hopefully this will result in the amelioration of the problem of atherosclerosis and of other diseases related to abnormalities of lipoprotein metabolism.